Chimera (genetics)
Encyclopedia
A chimera or chimaera is a single organism
(usually an animal
) that is composed of two or more different populations of genetically distinct cells
that originated from different zygote
s involved in sexual reproduction
. If the different cells have emerged from the same zygote, the organism is called a mosaic
. Chimeras are formed from four parent cells (two fertilized eggs or early embryos fused together). Each population of cells keeps its own character and the resulting organism is a mixture of tissues. Chimeras are typically seen in animals; there are some reports on human
chimerism. Plant chimeras
are discussed separately.
This condition is either inherited, or it is acquired through the infusion of allogeneic hematopoietic cells during transplantation
or transfusion
. In nonidentical twins, chimerism occurs by means of blood-vessel anastomoses. The likelihood of offspring being a chimera is increased if it is created via in vitro fertilization. Chimeras can often breed, but the fertility and type of offspring depends on which cell line gave rise to the ovaries or testes; varying degrees of intersex
uality may result if one set of cells is genetically female and another genetically male.
or zygote stages. This results in the development of an organism with intermingled cell lines. Put another way, the chimera is formed from the merging of two nonidentical twins
(although a similar merging presumably occurs with identical twins, but as their DNA is almost identical, the presence would not be immediately detectable in a very early (zygote or blastocyst) phase. As such, they can be male, female, or hermaphroditic.
As the organism develops, it can come to possess organ
s that have different sets of chromosome
s. For example, the chimera may have a liver
composed of cells with one set of chromosomes and have a kidney
composed of cells with a second set of chromosomes. This has occurred in humans, and at one time was thought to be extremely rare, though more recent evidence suggests that it is not as rare as previously believed.
This is particularly true for the marmoset
. Recent research shows most marmosets are chimerae, sharing DNA with their fraternal twins.
Most chimerae will go through life without realizing they are chimeras. The difference in phenotypes may be subtle (e.g., having a hitchhiker's thumb and a straight thumb, eyes of slightly different colors, differential hair growth on opposite sides of the body, etc.) or completely undetectable. Chimera may also show, under a certain spectrum of UV light, distinctive marks on the back resembling that of arrow points pointing downwards from the shoulders down to the lower back; this is one expression of pigment unevenness called Blaschko's lines
.
Affected persons may be identified by the finding of two populations of red cells or, if the zygotes are of opposite sex, ambiguous genitalia and hermaphroditism alone or in combination; such persons sometimes also have patchy skin, hair, or eye pigmentation (heterochromia
). If the blastocysts are of opposite sex, genitals of both sexes may be formed, either ovary
and testis, or combined ovotestes, in one rare form of intersexuality, a condition previously known as true hermaphroditism
.
Note that the frequency of this condition does not indicate the true prevalence of chimerism. Most chimerae composed of both male and female cells probably do not have an intersex condition, as might be expected if the two cell populations were evenly blended throughout the body. Often, most or all of the cells of a single cell type will be composed of a single cell line, i.e. The blood may be composed prominently of one cell line, and the internal organs of the other cell line. Genitalia produce the hormones responsible for other sex characteristics. If the sex organs are homogeneous, the individual will not be expected to exhibit any intersex traits.
Natural chimeras are almost never detected unless they exhibit abnormalities such as male/female or hermaphrodite characteristics or uneven skin pigmentation. The most noticeable are some male tortoiseshell cat
s or animals with ambiguous sex organs.
The existence of chimerism is problematic for DNA testing, a fact with implications for family and criminal law. The Lydia Fairchild
case, for example, was brought to court after DNA testing apparently showed that her children could not be hers. Fraud charges were filed against her and her custody of her children was challenged. The charge against her was dismissed when it became clear that Lydia was a chimera, with the matching DNA being found in her cervical tissue. Another case was that of Karen Keegan, who was also in danger of losing her children, after a DNA test for a kidney transplant seemed to show she wasn't the mother of her children.
The tetragametic state has important implications for organ or stem-cell
transplantation. Chimeras typically have immunologic tolerance to both cell lines.
anglerfish
and is in fact a natural and essential part of their life cycle. Once a male is born, it begins its search for a female. Using strong olfactory glands, the male searches until it locates a female anglerfish. The male, less than an inch in length, bites into her skin and releases an enzyme that digests the skin of his mouth and her body, fusing the pair down to the blood-vessel level. While this attachment has become necessary for the male's survival, it will eventually consume him, as both anglerfish fuse into a single hermaphroditic
individual. Sometimes in this odd ritual, more than one male will attach to a single female as a 'parasite'. They will both be consumed into the body of the larger female angler. Once fused to a female, the males will reach sexual maturity, developing large testicle
s as their other organs atrophy
. This process allows for sperm to be in constant supply when the female produces an egg, so that the chimeric fish is able to have a greater number of offspring.
and egg
cells) of an organism are not genetically identical to its own. It has recently been discovered that marmoset
s can carry the reproductive cells of their (fraternal) twin siblings, because of placental fusion during development. (Marmosets almost always give birth to fraternal twins.)
with a combined genetic makeup, or Hybridomas which, as with hybrids, result from fusion of two species' cells into a single cell and artificial propagation of this cell in the laboratory. Essentially, in a chimera, each cell is from either of the parent species, whereas in a hybrid and hybridoma, each cell is derived from both parent species. "Chimera" is a broad term and is often applied to many different mechanisms of the mixing of cells from two different species.
As with cloning, the process of creating and implanting a chimera is imprecise, with the majority of embryos spontaneously terminating. Successes, however, have led to major advancements in the field of embryology, as creating chimeras of one species with different physical traits, such as colour, has allowed researchers to trace the differentiation of embryonic cells through the formation of organ systems in the adult individual.
A major milestone in chimera experimentation occurred in 1984, when a chimeric geep was produced by combining embryo
s from a goat
and a sheep, and survived to adulthood. The creation of the "geep" revealed several complexities to chimera development. In implanting a goat embryo for gestation in a sheep, the sheep's immune system would reject the developing goat embryo, whereas a "geep" embryo, sharing markers of immunity with both sheep and goats, was able to survive implantation in either of its parent species.
In August 2003, researchers at the Shanghai Second Medical University in China reported that they had successfully fused human skin cells and dead rabbit
eggs to create the first human chimeric embryos. The embryos were allowed to develop for several days in a laboratory setting, then destroyed to harvest the resulting stem cell
s. In 2007, scientists at the University of Nevada
School of Medicine created a sheep whose blood contained 15% human cells and 85% sheep cells. The implications of increasingly realizable projects using human-animal hybrids for biopharmaceutical production, and potentially for producing cells or organs, have raised a host of ethical
and safety issues.
The general methods for creating chimeric mice can be summarized either by injection or aggregation of embryonic cells from different origins. The first chimeric mouse was made by Beatrice Mintz in the 1960s through the aggregation of eight cell stage embryos. Injection on the other hand was pioneered by Richard Gardner and Ralph Brinster who injected cells into blastocysts to create chimeric mice with germ lines fully derived from injected ES Cells.
Mouse embryos both periimplantation and post implantation can contribute to a chimera. It is post implantation that ES cells from the inner cell mass of a blastocyst can contribute to all cell lineages of a mouse including the germ line. ES cells are also a useful tool in chimeras because genes can be mutated in them through the use of homologous recombination, thus allowing gene targeting. Since this discovery occurred in 1999, ES cells have become a key tool in the generation of specific chimeric mice.
Two- to eight-cell-stage embryos are competent for making chimeras, since at these stages of development, the cells in the embryos are not yet committed to give rise to any particular cell lineage, and could give rise to the inner cell mass or the trophectoderm. In the case where two diploid eight-cell-stage embryos are used to make a chimera, chimersim can be later found in the epiblast, primitive, endoderm and trophectoderm of the mouse blastocyst. It is possible to dissect the embryo at other stages so as to accordingly give rise to one lineage of cells from an embryo selectively and not the other. For example, subsets of blastomeres can be used to give rise to chimera with specified cell lineage from one embryo. The Inner Cell Mass of a diploid blastocyst for example can be used to make a chimera with another blastocyst of eight-cell diploid embryo; the cells taken from the inner cell mass will give rise to the primitive endoderm and to the epiblast in the chimera mouse.
From this knowledge, ES cell contributions to chimeras have been developed. ES cells can be used in combination with eight-cell-and two-cell-stage embryos to make chimeras and exclusively give rise to the embryo proper. Embryos that are to be used in chimeras can further be genetically altered in order to specifically contribute to only one part of chimera. An example is the chimera built off of ES cells and tetraploid embryos, tetraploid embryos which are artificially made by electrofusion of two two-cell diploid embryos. The tetraploid embryo will exclusively give rise to the trophectoderm and primitive endoderm in the chimera
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
(usually an animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
) that is composed of two or more different populations of genetically distinct cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
that originated from different zygote
Zygote
A zygote , or zygocyte, is the initial cell formed when two gamete cells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo...
s involved in sexual reproduction
Sexual reproduction
Sexual reproduction is the creation of a new organism by combining the genetic material of two organisms. There are two main processes during sexual reproduction; they are: meiosis, involving the halving of the number of chromosomes; and fertilization, involving the fusion of two gametes and the...
. If the different cells have emerged from the same zygote, the organism is called a mosaic
Mosaic (genetics)
In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...
. Chimeras are formed from four parent cells (two fertilized eggs or early embryos fused together). Each population of cells keeps its own character and the resulting organism is a mixture of tissues. Chimeras are typically seen in animals; there are some reports on human
Human
Humans are the only living species in the Homo genus...
chimerism. Plant chimeras
Chimera (plant)
Chimeras in botany are usually single organisms composed of two genetically different types of tissue. They occur in plants, on the same general basis as with animal chimeras...
are discussed separately.
This condition is either inherited, or it is acquired through the infusion of allogeneic hematopoietic cells during transplantation
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
or transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
. In nonidentical twins, chimerism occurs by means of blood-vessel anastomoses. The likelihood of offspring being a chimera is increased if it is created via in vitro fertilization. Chimeras can often breed, but the fertility and type of offspring depends on which cell line gave rise to the ovaries or testes; varying degrees of intersex
Intersex
Intersex, in humans and other animals, is the presence of intermediate or atypical combinations of physical features that usually distinguish female from male...
uality may result if one set of cells is genetically female and another genetically male.
Tetragametic chimerism
Tetragametic chimerism is a form of congenital chimerism. This condition occurs through the fertilization of two separate ova by two sperm, followed by the fusion of the two at the blastocystBlastocyst
The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...
or zygote stages. This results in the development of an organism with intermingled cell lines. Put another way, the chimera is formed from the merging of two nonidentical twins
Twin
A twin is one of two offspring produced in the same pregnancy. Twins can either be monozygotic , meaning that they develop from one zygote that splits and forms two embryos, or dizygotic because they develop from two separate eggs that are fertilized by two separate sperm.In contrast, a fetus...
(although a similar merging presumably occurs with identical twins, but as their DNA is almost identical, the presence would not be immediately detectable in a very early (zygote or blastocyst) phase. As such, they can be male, female, or hermaphroditic.
As the organism develops, it can come to possess organ
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
s that have different sets of chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s. For example, the chimera may have a liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
composed of cells with one set of chromosomes and have a kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
composed of cells with a second set of chromosomes. This has occurred in humans, and at one time was thought to be extremely rare, though more recent evidence suggests that it is not as rare as previously believed.
This is particularly true for the marmoset
Marmoset
Marmosets are the 22 New World monkey species of the genera Callithrix, Cebuella, Callibella, and Mico. All four genera are part of the biological family Callitrichidae. The term marmoset is also used in reference to the Goeldi's Monkey, Callimico goeldii, which is closely related.Most marmosets...
. Recent research shows most marmosets are chimerae, sharing DNA with their fraternal twins.
Most chimerae will go through life without realizing they are chimeras. The difference in phenotypes may be subtle (e.g., having a hitchhiker's thumb and a straight thumb, eyes of slightly different colors, differential hair growth on opposite sides of the body, etc.) or completely undetectable. Chimera may also show, under a certain spectrum of UV light, distinctive marks on the back resembling that of arrow points pointing downwards from the shoulders down to the lower back; this is one expression of pigment unevenness called Blaschko's lines
Blaschko's lines
Blaschko's lines, also called the Lines of Blaschko, are skin lines invisible under normal conditions. They become apparent when some diseases of the skin or mucosa manifest themselves according to these patterns...
.
Affected persons may be identified by the finding of two populations of red cells or, if the zygotes are of opposite sex, ambiguous genitalia and hermaphroditism alone or in combination; such persons sometimes also have patchy skin, hair, or eye pigmentation (heterochromia
Heterochromia
In anatomy, heterochromia refers to a difference in coloration, usually of the iris but also of hair or skin. Heterochromia is a result of the relative excess or lack of melanin...
). If the blastocysts are of opposite sex, genitals of both sexes may be formed, either ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
and testis, or combined ovotestes, in one rare form of intersexuality, a condition previously known as true hermaphroditism
True hermaphroditism
True hermaphroditism is a medical term for an intersex condition in which an individual is born with ovarian and testicular tissue.There may be an ovary on one side and a testis on the other, but more commonly one or both gonads is an ovotestis containing both types of tissue.It is rare—so...
.
Note that the frequency of this condition does not indicate the true prevalence of chimerism. Most chimerae composed of both male and female cells probably do not have an intersex condition, as might be expected if the two cell populations were evenly blended throughout the body. Often, most or all of the cells of a single cell type will be composed of a single cell line, i.e. The blood may be composed prominently of one cell line, and the internal organs of the other cell line. Genitalia produce the hormones responsible for other sex characteristics. If the sex organs are homogeneous, the individual will not be expected to exhibit any intersex traits.
Natural chimeras are almost never detected unless they exhibit abnormalities such as male/female or hermaphrodite characteristics or uneven skin pigmentation. The most noticeable are some male tortoiseshell cat
Tortoiseshell cat
Tortoiseshell describes a coat coloring found mostly in female cats. Cats of this color are mottled, with patches of orange or cream and chocolate, black or blue. They are sometimes called torties...
s or animals with ambiguous sex organs.
The existence of chimerism is problematic for DNA testing, a fact with implications for family and criminal law. The Lydia Fairchild
Lydia Fairchild
Lydia Fairchild and her children are the subjects of a documentary called The Twin Inside Me .Lydia Fairchild was pregnant with her third child when she and the father of her children, Jamie Townsend, separated...
case, for example, was brought to court after DNA testing apparently showed that her children could not be hers. Fraud charges were filed against her and her custody of her children was challenged. The charge against her was dismissed when it became clear that Lydia was a chimera, with the matching DNA being found in her cervical tissue. Another case was that of Karen Keegan, who was also in danger of losing her children, after a DNA test for a kidney transplant seemed to show she wasn't the mother of her children.
The tetragametic state has important implications for organ or stem-cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
transplantation. Chimeras typically have immunologic tolerance to both cell lines.
Microchimerism
Microchimerism is the presence of a small number of cells that are genetically distinct from those of the host individual. Apparently, this phenomenon is related to certain types of autoimmune diseases, however, the mechanisms responsible for this relationship are unclear."Parasitic" chimerism in anglerfish
Chimerism occurs naturally in adult CeratioidCeratiidae
Sea devils are a family of deep-sea anglerfish otherwise known as Ceratiidae from the Greek keras, "horn", referring to the bioluminescent lure that projects from the fishes' forehead....
anglerfish
Anglerfish
Anglerfishes are members of the teleost order Lophiiformes . They are bony fishes named for their characteristic mode of predation, wherein a fleshy growth from the fish's head acts as a lure; this is considered analogous to angling.Some anglerfishes are pelagic , while others are benthic...
and is in fact a natural and essential part of their life cycle. Once a male is born, it begins its search for a female. Using strong olfactory glands, the male searches until it locates a female anglerfish. The male, less than an inch in length, bites into her skin and releases an enzyme that digests the skin of his mouth and her body, fusing the pair down to the blood-vessel level. While this attachment has become necessary for the male's survival, it will eventually consume him, as both anglerfish fuse into a single hermaphroditic
Hermaphrodite
In biology, a hermaphrodite is an organism that has reproductive organs normally associated with both male and female sexes.Many taxonomic groups of animals do not have separate sexes. In these groups, hermaphroditism is a normal condition, enabling a form of sexual reproduction in which both...
individual. Sometimes in this odd ritual, more than one male will attach to a single female as a 'parasite'. They will both be consumed into the body of the larger female angler. Once fused to a female, the males will reach sexual maturity, developing large testicle
Testicle
The testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system...
s as their other organs atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
. This process allows for sperm to be in constant supply when the female produces an egg, so that the chimeric fish is able to have a greater number of offspring.
Germline chimerism
Germline chimerism occurs when the germ cells (for example, spermSperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
and egg
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
cells) of an organism are not genetically identical to its own. It has recently been discovered that marmoset
Marmoset
Marmosets are the 22 New World monkey species of the genera Callithrix, Cebuella, Callibella, and Mico. All four genera are part of the biological family Callitrichidae. The term marmoset is also used in reference to the Goeldi's Monkey, Callimico goeldii, which is closely related.Most marmosets...
s can carry the reproductive cells of their (fraternal) twin siblings, because of placental fusion during development. (Marmosets almost always give birth to fraternal twins.)
Human chimeras
In 1953 a human chimera was reported in the British Medical Journal. A woman was found to have blood containing two different blood types. Apparently this resulted from cells from her twin brother living in her body. . More recently, a study found that such blood group chimerism is not rare. Another report of a human chimera was published in 1998, where a male human had some partially-developed female organs due to chimerism. He was conceived by in-vitro fertilization.Chimeras in research
In biological research, chimeras are artificially produced by selectively transplanting embryonic cells from one organism onto the embryo of another, and allowing the resultant blastocyst to develop. Chimeras are not hybrids, which form from the fusion of gametes from two species that form a single zygoteZygote
A zygote , or zygocyte, is the initial cell formed when two gamete cells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo...
with a combined genetic makeup, or Hybridomas which, as with hybrids, result from fusion of two species' cells into a single cell and artificial propagation of this cell in the laboratory. Essentially, in a chimera, each cell is from either of the parent species, whereas in a hybrid and hybridoma, each cell is derived from both parent species. "Chimera" is a broad term and is often applied to many different mechanisms of the mixing of cells from two different species.
As with cloning, the process of creating and implanting a chimera is imprecise, with the majority of embryos spontaneously terminating. Successes, however, have led to major advancements in the field of embryology, as creating chimeras of one species with different physical traits, such as colour, has allowed researchers to trace the differentiation of embryonic cells through the formation of organ systems in the adult individual.
A major milestone in chimera experimentation occurred in 1984, when a chimeric geep was produced by combining embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
s from a goat
Goat
The domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...
and a sheep, and survived to adulthood. The creation of the "geep" revealed several complexities to chimera development. In implanting a goat embryo for gestation in a sheep, the sheep's immune system would reject the developing goat embryo, whereas a "geep" embryo, sharing markers of immunity with both sheep and goats, was able to survive implantation in either of its parent species.
In August 2003, researchers at the Shanghai Second Medical University in China reported that they had successfully fused human skin cells and dead rabbit
Rabbit
Rabbits are small mammals in the family Leporidae of the order Lagomorpha, found in several parts of the world...
eggs to create the first human chimeric embryos. The embryos were allowed to develop for several days in a laboratory setting, then destroyed to harvest the resulting stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s. In 2007, scientists at the University of Nevada
University of Nevada, Reno
The University of Nevada, Reno , is a teaching and research university established in 1874 and located in Reno, Nevada, USA...
School of Medicine created a sheep whose blood contained 15% human cells and 85% sheep cells. The implications of increasingly realizable projects using human-animal hybrids for biopharmaceutical production, and potentially for producing cells or organs, have raised a host of ethical
Ethics
Ethics, also known as moral philosophy, is a branch of philosophy that addresses questions about morality—that is, concepts such as good and evil, right and wrong, virtue and vice, justice and crime, etc.Major branches of ethics include:...
and safety issues.
Mouse chimeras
Chimeric mice are important tools in biological research, as they allow the investigation of a variety of biological questions in an animal that has two distinct genetic pools within it. These include insights into such problems as the tissue specific requirements of a gene, cell lineage, and cell potential.The general methods for creating chimeric mice can be summarized either by injection or aggregation of embryonic cells from different origins. The first chimeric mouse was made by Beatrice Mintz in the 1960s through the aggregation of eight cell stage embryos. Injection on the other hand was pioneered by Richard Gardner and Ralph Brinster who injected cells into blastocysts to create chimeric mice with germ lines fully derived from injected ES Cells.
Mouse embryos both periimplantation and post implantation can contribute to a chimera. It is post implantation that ES cells from the inner cell mass of a blastocyst can contribute to all cell lineages of a mouse including the germ line. ES cells are also a useful tool in chimeras because genes can be mutated in them through the use of homologous recombination, thus allowing gene targeting. Since this discovery occurred in 1999, ES cells have become a key tool in the generation of specific chimeric mice.
Underlying biology
The ability to make mouse chimeras comes from an understanding of early mouse development. Between the stages of fertilization of the egg and the implantation of a blastocyst into the uterus, different parts of the mouse embryo retain the ability to give rise to a variety of cell lineages. Once the embryo has reached the blastocyst stage, it is composed of several parts, mainly the trophectoderm, the inner cell mass, and the primitive endoderm. Each of these parts of the blastocyst gives rise to different parts of the embryo; the inner cell mass gives rise to the embryo proper, while the trophectoderm and primitive endoderm give rise to extra embryonic structures that support growth of the embryo.Two- to eight-cell-stage embryos are competent for making chimeras, since at these stages of development, the cells in the embryos are not yet committed to give rise to any particular cell lineage, and could give rise to the inner cell mass or the trophectoderm. In the case where two diploid eight-cell-stage embryos are used to make a chimera, chimersim can be later found in the epiblast, primitive, endoderm and trophectoderm of the mouse blastocyst. It is possible to dissect the embryo at other stages so as to accordingly give rise to one lineage of cells from an embryo selectively and not the other. For example, subsets of blastomeres can be used to give rise to chimera with specified cell lineage from one embryo. The Inner Cell Mass of a diploid blastocyst for example can be used to make a chimera with another blastocyst of eight-cell diploid embryo; the cells taken from the inner cell mass will give rise to the primitive endoderm and to the epiblast in the chimera mouse.
From this knowledge, ES cell contributions to chimeras have been developed. ES cells can be used in combination with eight-cell-and two-cell-stage embryos to make chimeras and exclusively give rise to the embryo proper. Embryos that are to be used in chimeras can further be genetically altered in order to specifically contribute to only one part of chimera. An example is the chimera built off of ES cells and tetraploid embryos, tetraploid embryos which are artificially made by electrofusion of two two-cell diploid embryos. The tetraploid embryo will exclusively give rise to the trophectoderm and primitive endoderm in the chimera
Methods of production
There are a variety of combinations that can give rise to a successful chimera mouse and — according to the goal of the experiment — an appropriate cell and embryo combination can be picked; they are generally but not limited to diploid embryo and ES cells, diploid embryo and diploid embryo, ES cell and tetraploid embryo, diploid embryo and tetraploid embryo, ES cells and ES cells. The combination of embryonic stem cell and diploid embryo is a common technique used for the making of chimeric mice, since gene targeting can be done in the embryonic stem cell. These kinds of chimeras can be made through either aggregation of stem cells and the diploid embryo or injection of the stem cells into the diploid embryo. If embryonic stem cells are to be used for gene targeting to make a chimera, the following procedure is common: a construct for homologous recombination for the gene targeted will be introduced into cultured mouse embryonic stem cells from the donor mouse, by way of electroporation; cells positive for the recombination event will have antibiotic resistance, provided by the insertion cassette used in the gene targeting; and be able to be positively selected for. ES cells with the correct targeted gene are then injected into a diploid host mouse blastocyst. These injected blastocysts are then implanted into a pseudo pregnant female surrogate mouse which will bring the embryos to term and give birth to a mouse whose germline is derived from the donor mouse's ES cells. This same procedure can be achieved through aggregation of ES cells and diploid embryos, diploid embryos are cultured in aggregation plates in wells were single embryos can fit, to these wells ES cells are added the aggregates are cultured until a single embryo is formed and has progressed to the blastocyst stage, and can then be transferred to the surrogate mouse.Legislation
The US and Western Europe have strict codes of ethics and regulations in place that expressly forbid certain subsets of experimentation using human cells, though there is a vast difference in the regulatory framework. In May 2008, a robust debate in the House of Commons of the United Kingdom on the ethics of creating chimeras with human stem cells led to the decision that embryos would be allowed to be made in laboratories, given that they would be destroyed within the first 14 days. No such foundation has been set for chimera research regulation in the US.See also
- Blaschko's linesBlaschko's linesBlaschko's lines, also called the Lines of Blaschko, are skin lines invisible under normal conditions. They become apparent when some diseases of the skin or mucosa manifest themselves according to these patterns...
- Chimera (plant)Chimera (plant)Chimeras in botany are usually single organisms composed of two genetically different types of tissue. They occur in plants, on the same general basis as with animal chimeras...
- Chimerism in human intersexuality
- Genetic chimerism in fictionGenetic chimerism in fictionHuman genetic chimerism, which can not only cause a wide range of illnesses but also lead to the same person having more than one profile in genetic fingerprinting, has served as a plot device in many works of fiction...
- Lydia FairchildLydia FairchildLydia Fairchild and her children are the subjects of a documentary called The Twin Inside Me .Lydia Fairchild was pregnant with her third child when she and the father of her children, Jamie Townsend, separated...
- Mosaic (genetics)Mosaic (genetics)In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...
- ParahumanParahumanA parahuman or para-human is a term used to describe a human-animal hybrid or chimera. Scientists have done extensive research into the mixing of genes or cells from different species, e.g...
s - Vanishing twinVanishing twinA vanishing twin, also known as fetal resorption, is a fetus in a multi-gestation pregnancy which dies in utero and is then partially or completely reabsorbed by the mother or twin....
- Conjoined twinsConjoined twinsConjoined twins are identical twins whose bodies are joined in utero. A rare phenomenon, the occurrence is estimated to range from 1 in 50,000 births to 1 in 100,000 births, with a somewhat higher incidence in Southwest Asia and Africa. Approximately half are stillborn, and a smaller fraction of...